This application claims the priority of Korean Patent Application No. 2003-5486, filed on Jan. 28, 2003, in the Korean Intellectual Property Office, the disclosure of which is incorporated herein in its entirety by reference.
1. Field of the Invention
The present invention relates to a method of treating a surface of a substrate used in a biological reaction system, and more particularly, to a method of chemically treating a surface of a substrate used in a biological reaction system to prevent biological molecules from adhering to the surface.
2. Description of the Related Art
Most miniaturized labs-on-a-chip consist of a DNA extraction or sample preparation unit, a DNA amplification unit, and a DNA detection unit. The DNA amplification unit includes a thermal cycler that repeats heating and cooling to a denaturation temperature, an annealing temperature, and an extension temperature to amplify DNA. Conventionally, a polymerase chain reaction (PCR) system has been made of a polypropylene e-tube. Recently, silicon or glass has been used more and more for the PCR reactor. The surface area per volume of the PCR reactor increases more and more. As a result, non-specific binding of PCR reactants and products to the surface of the PCR reactor occurs more frequently, lowering the yield of the PCR reaction.
Silicon and glass can be utilized as materials for various biochemical reactors, in addition to the PCR reactor. Accordingly, these biochemical reactors also suffer from non-specific binding of biomolecules to the silicon or glass surface and yields low from the biochemical reaction. Therefore, in biochemical reactors made of silicon or glass with a PCR reaction therein, it is required to treat a silicon or glass surface of the reactor to prevent non-specific binding of biomolecules.
Exemplary conventional suggestions for preventing a non-specific binding of biomolecules to the surface of a silicon structure, including a PCR reactor, where biochemical reactions take place, include forming a SiO2 film on the surface of the silicon structure by oxidization at high temperature and depositing a polymer solution that can suppress such non-specific binding to the surface of the silicon substrate.
U.S. Pat. No. 6,475,722 discloses the formation of a silicon oxide film or a silicon nitride film on a silicon surface of a DNA processing system, which includes PCR reactor, to prevent a non-specific absorption of DNA or other biochemical molecules to the silicon surface.
U.S. Pat. No. 6,261,431 discloses the addition of bovine serum albumin (BSA) into a PCR buffer. A method of adding a dispersant, such as Tween 20, together with BSA to lower surface energy of the buffer was also suggested (Ivonne Schneegab et al., “Miniaturized flow-through PCR with different types in a silicon chip thermocycler,” Lab-on-a-chip, Vol.1, p. 42-49, 2001)
U.S. Pat. No. 6,156,389 discloses a method of processing a silicon or glass surface to be hydrophobic, in which the silicon or glass surface is coated with a solution of a fluorinated monomer that contains 3 to 20 carbon atoms and a trifluoromethyl group at at least one terminal by spraying or dipping. However, the patent aims only at making the surface hydrophobic and, evidently from many experimental data, rather leads to a lower yield from the PCR reaction compared to before the surface treatment that results in only a kind of fluorinated hydrocarbon film (Nucleic Acids Research, “Chip PCR. 1. Surface Passivation of Microfabricated Silicon-glass Chips for PCR”, 24, 1996, 375-379).
In addition, there is a method of using a polymer solution which can suppress such a non-specific adsorption. This method involves injecting the polymer solution into a miniaturized 3D chip structure to coat a chip surface and rinsing and drying processes. These processes are experimentally complicate to perform and the results are not reproducible (Nucleic Acids Research, 24, 1996, “Chip PCR.1. Surface Passivation of Microfabricated Silicon-glass Chips for PCR”, 375-379; Clinical Chemistry, 41, 1995, “Thermal Cycling and Surface Passivation of Micromachined Devices for PCR Chip”, 1367-1368).